The long-term complications of Type 2 Diabetes Mellitus (T2DM) include structural and functional impairments to the microvasculature. In skeletal muscle, these result in reduced blood flow for glucose disposal and to support physical activity, imperiling both local tissue and overall health. However, there are no non-invasive methods for specifically studying skeletal muscle microvascular function used in routine clinical practice. The overall objective of the proposed studies is to develop proton density- and blood oxygenation level-dependent (BOLD)- sensitive magnetic resonance imaging (MRI) techniques for studying skeletal muscle microvascular function non-invasively. Specific Aim 1 is to test the hypothesis that analysis of post-isometric contraction changes in proton density-weighted MRI signals will reproducibly and reliably distinguish between T2DM patients with microvascular disease and healthy subjects. We currently use short- and long- gradient echo MRI signals to follow blood volume and oxygenation changes following brief maximal isometric contractions. We have adapted our current protocols so as to provide greater sensitivity to the attenuated total blood flow responses and delayed blood flow kinetics in T2DM. Specific Aim 2 is to use post-contraction changes in proton density-weighted MRI signal transients to assess microvascular function in T2DM patients after initial diagnosis and during 3 months of clinical intervention according to current standards-of-care. This will allow us to examine the feasibility of using these measures to assess microvascular responses to improved glycemic control without interfering with patient care. Successfully accomplishing these aims will improve the health of persons with T2DM by providing new non-invasive techniques for assessing peripheral microvascular function. Type 2 diabetes is a serious disorder in which the body can not regulate blood sugar levels properly. One of the long-term complications of Type 2 diabetes is reduced blood flow to the muscles. This leads to even worse blood sugar control and possibly to very serious complications such as limb amputation. In these studies we will be developing new methods for studying blood flow to muscles non-invasively. [unreadable] [unreadable] [unreadable]